I intend to investigate aging related physiological and pathological changes in kokanee salmon (Oncorhynchus nerka kennerlyi), which are also characteristic of human Alzheimer's disease. These include cerebral beta amyloid (Abeta) plaque formation, chronically elevated cortisol and accelerated neurodegeneration. The hypothesis that chronically elevated cortisol and starvation (normal kokanee spawning conditions) can induce neurodegeneration and Abeta plaque formation will be tested by injecting absorbable pellets of cortisol and forcing starvation in hatchery reared kokanee salmon. The physiological effects of natural cortisol elevation during upstream migration and spawning will also be examined by blocking cortisol receptors with RU-486 administered in absorbable pellets. The amyloid cascade hypothesis will be investigated in kokanee salmon by administering an inhibitor of Abeta production during migration and spawning. Lastly pathological similarities in neurodegeneration and Abeta plaque formation between spawning kokanee salmon, older humans and humans with AD will be investigated by immunohistochemistry.